Differential expression of thymic DNA repair genes in low-dose-rate irradiated AKR/J mice

We previously determined that AKR/J mice housed in a low-dose-rate (LDR) (137Cs, 0.7 mGy/h, 2.1 Gy) gamma-irradiation facility developed less spontaneous thymic lymphoma and survived longer than those receiving sham or high-dose-rate (HDR) (137Cs, 0.8 Gy/min, 4.5 Gy) radiation. Interestingly, histopathological analysis showed a mild lymphomagenesis in the thymus of LDR-irradiated mice. Therefore, in this study, we investigated whether LDR irradiation could trigger the expression of thymic genes involved in the DNA repair process of AKR/J mice. The enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways showed immune response, nucleosome organization, and the peroxisome proliferator-activated receptors signaling pathway in LDR-irradiated mice. Our microarray analysis and quantitative polymerase chain reaction data demonstrated that mRNA levels of Lig4 and RRM2 were specifically elevated in AKR/J mice at 130 days after the start of LDR irradiation. Furthermore, transcriptional levels of H2AX and ATM, proteins known to recruit DNA repair factors, were also shown to be upregulated. These data suggest that LDR irradiation could trigger specific induction of DNA repair-associated genes in an attempt to repair damaged DNA during tumor progression, which in turn contributed to the decreased incidence of lymphoma and increased survival. Overall, we identified specific DNA repair genes in LDR-irradiated AKR/J mice.

Protection by live Mycobacterium habana vaccine against Mycobacterium tuberculosis H37Rv challenge in mice.

BACKGROUND & OBJECTIVES: In recent years the efficacy of BCG vaccine against tuberculosis has been questioned and there is no alternative vaccine available. Several strategies are being applied to get a satisfactory vaccine. Two approaches are generally considered: the subunit vaccines and the whole cell vaccines. The objective of this investigation was to evaluate an avirulent mycobacteria, Mycobacterium habana, as a whole cell vaccine to protect mice from infection of M. tuberculosis H37Rv. METHODS: AKR and immunocompromised SJL/J mice were immunized with live M. habana vaccine. These mice were challenged with M. tuberculosis H37Rv eight weeks later along with unimmunized control mice. Protection by M. habana vaccine was measured through several parameters, which included survival of challenged mice, dissemination of challenge strain and histopathology of lung tissues. RESULTS: M. habana vaccinated animals were healthier than the unvaccinated mice after challenge with M. tuberculosis and survived with significant increase in mean survival time. The viable count of challenge strain was at least 100-fold less in vaccinated mice than the control mice. The lung tissues in unvaccinated mice showed marked bronchopneumonia with clusters of acid fast bacilli, whereas vaccinated mice showed small areas of damage and evidence of protection subsequently. INTERPRETATION & CONCLUSION: It may be concluded from the evidence presented here that mice vaccinated with M. habana were protected from challenge with M. tuberculosis in both normal and immunocompromised states.

Differences between hepatic and biliary lipid metabolism and secretion in genetically gallstone-susceptible and gallstone-resistant mice / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate differences between hepatic and biliary lipid metabolism and secretion of genetically gallstone-susceptible (C57L) and resistant (AKR) mice and the mechanism of cholesterol gallstone formation.</p><p><b>METHODS</b>The inbred C57L and AKR mice were fed a lithogenic diet containing 15% fat, 1.25% cholesterol and 0.5% cholic acid for four weeks. Hepatic cholesterol content and secretion rates of biliary lipids, as well as phenotypes of the liver and gallbladder were determined and examined before and after the feeding of the lithogenic diet.</p><p><b>RESULTS</b>Both before and after ingestion of the lithogenic diet, hepatic secretion rates of all biliary lipids in C57L mice were markedly higher than that of AKR mice (P < 0.05, P < 0.01, respectively), whereas hepatic cholesterol contents of C57L mice were significantly lower than that of AKR mice (P < 0.05). Furthermore, after consumption of the lithogenic diet, the increase in hepatic secretion rate of biliary cholesterol in C57L mice was significantly higher than that in AKR mice (P < 0.01). Cholesterol gallstones formed in C57L mice and fatty livers developed in AKR mice.</p><p><b>CONCLUSIONS</b>Biliary cholesterol hypersecretion is the key pathophysiological defect of gallstone formation, lith genes have effects on biliary cholesterol hypersecretion and susceptibility to cholesterol gallstone formation in C57L mice. Lithogenic bile is formed at the canalicular membrane and precedes the development of cholesterol gallstones. It is most likely that cholesterol and bile acid hyposecretion make the AKR strain susceptible to the development of fatty livers and resistant to gallstone formation.</p>

Telomerase activity in thymomas and mammary gland adenocarcinomas induced by polyoma virus in AKR mice

Telomerase is an enzyme that stabilizes telomere lenght in transformed cells and tumors. Its role in tumor development is far from clear. In this paper, a new experimental model to study telomerase activity during tumorigenesis is presented. After infection with Polyoma virus, AKR mice developed thymomas and mammary gland adenocarcinomas. Polyoma antigens were observed by the peroxidase-antiperoxidase technique on tissue sections, and by Western blot on tumor extracts. The TRAP assay was performed to detect telomerase activity. It was not present in normal mammary gland, but it was positive in mammary gland adenocarcinomas. A different pattern was seen in thymic tissues: normal thymus had higher telomerase activity than thymomas. The incubation of thymoma extracts with normal thymus extracts decreased telomerase activity in the latter. These results demonstrate two different patterns of telomerase activity in tumors induced by Polyoma virus, and suggest the presence of telomerase inhibitory factors in thymomas.

A maternally-inherited alteration in the T cell repertoire of balb/c mice

Se ha demostrado que los virus exógenos del tumor mamario murino (MMTV) transmitidos por leche, inducen la expresión de diferentes superantígenos en los huéspedes infectados. Cada uno de estos superantígenos es capaz de inducir la deleción clonal progresiva de las células T portadoras de determinados elementos Vß de su receptor (TCR). En este trabajo se describe la existencia de una alteración en el repertorio T de los ratones BALB/c de una colonia. Dicha alteración, transmitida por vía materna, involucra la deleción de las células T CD4+ que expresan las cadenas Vß2 y Vß14 del TCR y correlaciona con una alta incidencia de tumores de mama. Estos resultados indican la transmisión materna de un superantígeno(s), probablemente asociado a la presencia de virus MMTV en la leche

Desenvolvimento do Schistosoma mansoni na cavidade peritoneal de camundongos da linhagem AKR/J / Schistosoma mansoni development in the peritoneal cavity of inbred AKR/J mice

Cercariae of Schistosoma mansoni after intraperitoneal inoculation, developed and reached the sexual maturation in that site with egg production. In the AKR/J strain of mice, 7.7 of the peritoneal recovered females showed normal eggs in the uterus. No evidence of hemoglobinic pigment in their digestive tract was observed in the peritoneal recovered parasites from both strains (AKR/J and SWISS). This fact suggests that the parasites can develop without red blood cells ingestion. On the other hand, the development of the parasite with egg production in the peritoneal cavity of the AKR/J mouse reinforces the data that the lung phase is not necessary for the development of the parasite.

Electrokinetic behaviour of subpopulations of T lymphocytes in allografted mice.

In AKR(H-2k) mice transplanted with DBA/2(H-2d) skin grafts, the mean electrophoretic mobilities (EPM) of total lymph node cells (LNC) and T cells were significantly reduced. Subpopulations of T lymphocytes, viz. CD4- (CD8- (CD4+) T cells were obtained by depletion treatment of T cells with monoclonal antibodies specific for these surface antigens and complement. Determination of EPM of these two subpopulations revealed that the electrokinetic change following immunostimulation equally afflicted these two subpopulations. These data thus confirmed that CD4+ as well as CD8+ T cells were activated in MHC unmatched allograft rejection.

Ontogenia del reconocimiento T de antígenos de histocompatibilidad propios: influencias parenterales / Ontogeny of the T recognition of self histocompatibility antigens: parenteral influences

Se investigó la existencia de influencias parentales que pudieran afectar el recononcimiento de los antígenos de histocompatibilidad propios en la progenie. Se pudo observar que 1) tanto las células de hígado fetal como los esplenocitos y timocitos de hbridos F1 recién nascidos diferen en su capacidad de regular las reacciones alorreactivas parentales dirigidas a antígenos de histocompatibilidad propios según éstos sean de origen materno o paterno. Son capaces de suprimir - hasta el día 5 después del nacimiento- las reacciones sistémicas y locales de GvH inducidas con células maternas mientras que no suprimen aquellas desencadenadas con células paternas; 2) la falta de actividad supresora correlaciona con la aparición de células tímicas con actividad contrasupresora; 3) los esplenocitos de híbridos F1 adultos recíprocos diferen significativamente en su capacidad para estimular la proliferación de células T en reacciones de cultivo mixto singeneico; 4) el amamantamiento de los híbridos F1 con hembras provenientes de la cepa paterna es capaz de inducir alteraciones permanentes en la capacidad estimulatorra de los esplenocitos; el patrón estimulatorio de los esplenocitos de híbridos anamantados por nodrizas de la cepa híbridos F1 recíprocos adultos diferen en su respuesta a antígenos convencionales presentados en el contexto de los antígenos la parentales, estando la lactancia centralmente involucrada. Se discuten los posibles mecanismos involucrados

Autonomic nervous system regulation of murine immune responses as assessed by local surgical sympathetic and parasympathetic denervation

En ratones sometidos a gangliectomia simpática cervical superior (SCGx) unilateral se estudió el efecto de la desnervación local sobre la respuesta imune de ganglios linfáticos submaxilares (SmLN). El contenido de norepinefrina (NE) de SmLN disminuyó en un 90% a los 7-20 dias luego de la SCGx uni o bilateral. Los SmLN ipsilaterales de ratones SCGx unilateralmente 10-20 días antes e inyectados i.d. o i.p. con eritrocitos de carnero mostraron una respuesta de células formadoras de placa (PFC) significantivamente mayor que el control invervado contralateral. En ratones inyectados con eritrocitos de carnero en al fase temprana de parálisis neural simpática (2 h luego de la SCGx), se detectó una respuesta PFC aumentada mientras que durante la fase de degeneración anterógrada de los terminales (6-24 h luego de SCGx), se observó una disminucióm crecimente de PFC. En ratones crónicamente SCGx se detectó también un aumento significativo en la hipersensibilidad por contacto y reacción alogeneica retardada en al oreja ipsilateral a la operación. Al inyectar células de SmLN desnervados a F1 de (BALB/c x C57Bl/6) o de (BALB/c x AKR) se obtuvbieron índices esplénicos significativamente mayores que los observados luego de inyectar células controles. La estimulación mitogénica en diferentes protocolos experimentales no resultó en diferencias significativas entre SmLN desnervados e inervados. Luego de la descentralización local por sección unilateral del tronco lingual-cuerda del tímpano, los SmLN ipsilaterales exhibieron menor respuesta PFC 8-28 días luego de la cirugía. Estos resultados indican función modulatoria del sistema nervioso autónomo en la respuesta inmune

Estudo imunopatológico de camundongos de seis diferentes linhagens isogênicas à infecçäo por três tipos de cepas do "Trypanosoma cruzi" / Immunepathologic study of mice of six embread strains infested by three different Trypanosoma cruzi strains

Foi feito um estudo da infecçäo por três diferentes cepas do trypanosoma cruzi em camundongos isogênicos de seis diferentes linhagens com o objetivo de estudar a reposta imunológica humoral e celular e comparar o comportamento das cepas do T. cruzi em linhagens de camundongos geneticamente distintas. As linhagens isogênicas de camundongos foram: A/J,AKR,BALB/c,C3H/He,C57BL/10 e DBA/1. As cepas do T. cruzi classificadas em três tipos de acordo com seus caracteres morfobiológicos, isoenzimáticos e antigênicos foram: cepa Peruana (Tipo I), cepa 21 DF (Tipo II) e cepa Colombiana (Tipo III). O inóculo utilizado em todos os grupos experimentais foi de 100.000 tripomastigotas sangüícolas. Foram utilizados como parâmetros para o acompanhamento da infecçäo: os níveis de parasitemia, os índices de mortalidade e o cálculo da resistência através da édia harmônica da sobrevida, os níveis das fraçöes das imunoglobulinas séricas: IgG1,IgG2a,IgG2b e IgM, avaliados pela técnica de imunodifusäo radial quantitativa; titulaçäo de anticorpos específicos pela imunofluorescência indireta com antígeno específico; teste cutâneocom antígeno específico. Os dados obtidos foram submetidos à análise estatística aplicando-se a análise da variância para a compara;cäo enter os diversos parâmetros. A associaçäo entre os diversos dados obtidos foi estudade pelo teste da adequaçäo da curva para uma correlaçäo linear. Os animais sacrificados durante o curso do experimento, a partir do 5o.dia de infecçäo para estudo histopatológico. O estado reacional do baço foi avaliado histologicament e pela relaçäo peso baço/peso corporal. A avaliaçäo da resistência das diferentes linhagens através da comparaçäo, pela análise da variância, da média harmônica da sobrevida mostrou que, na infecçäo pela cepa Peruana (Tipo I) näo houve diferença significante entre as várias linhagens sendo todas muito susceptíveis a este tipo de cepa. Na infecçäo pela cepa de Tipo II (21 SF) a linhagem AKR é extremamente susceptível e a B10 muito resistente. As demais formam um espectro bem definido quanto à susceptibilidade que difere do espectro que se apresenta à infecçäo pela cepa de Tipo III (Colombiana). Nesta última os animais DBA säo os mais resistentes e os A/J os mais susceptíveis. Comparando-se a infecçäo pelas cepas de Tipos II e III, verifica-se que, com exceçäo da linhagem AKR, as outras säo mais resistentes à infecçäo pela cepa 21 SF do que pela Colombiana. Os níveis de parasitemia variam conforme a linhagem do camundondo porém o perfil da curva parasitêmica é característico par o tipo de cepa empregado, mantendo-se constante, independentemente da linhagem. Entre os animais das linhagens mais resistentes há uma correlaçäo entre o maior grau de resistência e os menores níveis parasitêmicos, à infecçäo com as cepas 21 DG e Colombiana. Esta correlaäo näo é entretanto observada entre os animais mais susceptíveis podendo-se observar animais com alta taxa de mortalidade e com uma média parasitêmica baixa. O oposto também pode seer observado em que algumas linhagens resistentes podem apresentar níveis elevados de parasitemia e elevada sobrevida...